Chemical Properties
White powder
History
Penicillin was discovered by chance in 1928 by Alexander Fleming. He
observed that the growth of a bacteria culture was inhibited by a fungus
Penicillum notatum. He published his results but did not pursue its
industrial development actively. Ten years later, H. Florey and coworkers
had produced enough purified penicillin to treat just one patient.
This test, however, was sufficient to prove that it was a viable drug.
From then on many people and companies participated in the development
of new fermentation technologies, new microorganisms, new downstream
processing, and so on to make a large-scale production possible.
Penicillin did not only change the medical world, but also the fermentation
technology. The naturally growing (wild type) Penicillum notatum
produced penicillin with a yield of 10 mg/L. Therefore, the first task was
the search for a more productive species. Eventually, Penicillium chrysogenum
was identified as the most productive species. To enhance penicillin
production further, the old method of growing Penicillum mold on
the surface of the medium in liter-sized flasks was replaced by fermentation
in large aerated tanks. This allowed the mold to grow throughout
the entire tank and not just on the surface of the medium. Today,
penicillin and other antibiotics are produced in large-scale fermenters
holding several hundred cubic meters of medium and the yield has
increased 5000 fold to 50 g/L.
Uses
Penicillin G is a narrow spectrum natural antibiotic. It is effective against
Streptococcus pneumoniae, groups A, B, C and G streptococci, nonenterococcal group D streptococci, viridans group streptococci, and non-penicillinase producing staphylococcus. It has been used to study the diagnostic and therapeutic implications of gentamicin-resistant
Enterococcus faecalis sequence type 6 with reduced penicillin susceptibility and in cell culture both alone and combined with streptomycin and other antibiotics.
Uses
Penicillin G sodium salt is used as a β-lactam antibiotic. Penicillin G can be used as a selective agent in several types of isolation media. It has been used to study the diagnostic and therapeutic implications of gentamicin-resistant Enterococcus faecalis sequence type 6 with reduced penicillin susceptibility and in cell culture both alone and combined with streptomycin and other antibiotics.
Uses
Sodium salt of Penicillin G, an antibacterial, antimicrobial medication. Used in the treatment of pneumococcus and streptococcus bacterial infections.
Definition
penicillin: An antibiotic derivedfrom the mould Penicillium notatum;specifically it is known as penicillin Gand belongs to a class of similar substancescalled penicillins. They producetheir effects by disruptingsynthesis of the bacterial cell wall,and are used to treat a variety of infectionscaused by bacteria.
brand name
Bicillin all purpose;Ceilipen;Cidan-cilina;Cilipen;Coliriocilina;Crisocilin-g;Crystamycin;Crystapen g;Demosa casi penicilina;Dermosa cusipenicilina;Falaper;Gonoper;Hormocillin forte;Ilcocillin;Juvanesta;Lasacilina;Liademycin;M-cillin b;Monocillin;Natricilin;P.g.a.;Paclia g;Patosica;Penibiot;Penicilina klari;Penilevel;Penimiluy;Peniroger;Penitasa "450" simple;Sancilin;Saniciline;Servipan;Sk-penicillin g;Sodiopen;Sodipen;Tabillin;Therapen-na;Triplopen;Unicilina sodia.
World Health Organization (WHO)
WHO Comment(Benzylpenicillin sodium topical preparations): Benzylpenicillin sodium, one of the first penicillin derivatives to
be used in medicine, was introduced in the early 1940s. Topical preparations
intended for use on the skin have been associated with allergic rashes and are in
general no longer acceptable. However, topical preparations for specialized use, in
particular in the eye and on open wounds, are available in many countries.
Injectable preparations of benzylpenicillin are included in the WHO Model List of
Essential Drugs.
World Health Organization (WHO)
Penicillin is listed separately in the WHO
Model List of Essential Drugs.
General Description
White to slightly yellow crystalline powder with a faint odor. pH (10% solution) 5.5-7.5.
Air & Water Reactions
Water soluble.
Reactivity Profile
Penicillin G sodium salt is hygroscopic. Penicillin G sodium salt is incompatible with acids, oxidizing agents (especially in the presence of trace metals), heavy metal ions such as copper, lead, zinc and mercury; glycerol, sympathomimetic amines, thiomersal, wood alcohols, cetostearyl alcohol, hard paraffins, macrogols, cocoa butter and many ionic an nonionic surface-active agents. Penicillin G sodium salt is also incompatible with alkalis, compounds leached from vulcanized rubber, hydrochlorides of tetracyclines and organic peroxides. Other incompatibilities include reducing agents, alcohols, other hydroxy compounds, self-emulsifying stearyl alcohol, emulsifying wax, lanolin, crude cholinesterated bases, glycol, sugars, amines, aminacrine hydrochloride, ephedrine, procaine, rubber tubing, thiamine hydrochloride, zinc oxide, oxidized cellulose, iodine, iodides, thiols, chlorocresol and resorcinol. Penicillin G sodium salt may also be incompatible with naphthalene oils and vitamin B.
Fire Hazard
Flash point data for Penicillin G sodium salt are not available; however, Penicillin G sodium salt is probably combustible.
Biochem/physiol Actions
Mode of Action: Penicillin G acts by inhibiting cell wall synthesis through binding to penicillin binding proteins (PBPs), inhibiting peptidoglycan chain cross-linking.Antimicrobial spectrum: This product is active against gram-positive and gram-negative bacteria.
Safety Profile
Poison by intracerebral,parenteral, and intramuscular routes. Moderately toxic viaintravenous route. Mildly toxic by ingestion. Experimentalteratogenic and reproductive effects. Questionablecarcinogen with experimental tumorigenic data. Whenheated to
Synthesis
Penicillin can be made by many types of Penicillium fungi, and also by a few types of
Asperigillus fungi. In industrial conditions, culture fluids are made that contain more than 30
mg/mL of penicillin. About two-thirds of the produced penicillin is used for making 6-APA.
Despite the possibility of pure chemical deacylation, the most prospective way of making
6-APA is an enzymatic method of hydrolyzing benzylpenicillin molecules using immobilized penicyllinamidase, an enzyme isolated from practically all penicillin-producing fungi.
Purification Methods
Purify the salt by dissolving it in a small volume of MeOH (in which it is more soluble than EtOH) and treating gradually with ~5 volumes of EtOAc. This gives an almost colourless crystalline solid (rosettes of clear-cut needles) and recrystallising twice more if slightly yellow in colour. The salt has also been conveniently recrystallised from the minimum volume of 90% Me2CO and adding an excess of absolute Me2CO. A similar procedure can be used with wet n-BuOH. If yellow in colour, then dissolve (~3.8g) in the minimum volume of H2O (3mL), add n-BuOH and filter through a bed of charcoal. The salt forms long white needles on standing in a refrigerator overnight. More crystals can be obtained on concentrating the mother liquors in vacuo at 40o. A further recrystallisation (without charcoal) yields practically pure salt. A good preparation has ~600 Units/mg. The presence of H2O in the solvents increases the solubility considerably. The solubility in mg/100mL at 0o is 6.0 (Me2CO), 15.0 (Me2CO/0.5% H2O), 31.0 (Me2CO/1.0% H2O), 2.4 (methyl ethyl ketone), 81.0 (n-butanol) and 15.0 (dioxane at 14o). Alternatively it is dissolved in H2O (solubility is ~10%), filtered if necessary and precipitated by addition of EtOH and dried in a vacuum over P2O5. A sample can be kept for 24hours at 100o without loss of physiological activity. It also crystallises from MeOH/EtOAc. [IR: Barnes et al. Anal Chem 19 620 1947, The Chemistry of Penicillin (Clarke, Johnson and Robinson eds.) Princeton University Press, Princeton NJ, Chapter V 85 1949, Beilstein 27 III/IV 5861.]
